Antibiotic resistance (AR) is a critical public health threat and one of the greatest challenges of the 21st century. In an estimate of 2019, nearly 700.000 infections and 33.000 attributable deaths from multi-drug-resistant bacteria (MDRB) have occurred in Europe in 2015. The gastrointestinal tract is a large reservoir for MDRB, and the gut microbiota can harbor a collection of AR genes, called gut resistome. Preliminary nonrandomized evidence suggests that fecal microbiota transplant (FMT) could be a promising treatment option to eradicate MDRB, but established evidence, as well as mechanisms that underpin this therapeutic pathway, are still unavailable. Leveraging our expertise in FMT (OU1), microbiome (OU2) and MDRB (OU3), we aim to evaluate the efficacy of FMT (from donors with limited presence of AR genes) in eradicating intestinal MDRB through a randomized controlled trial and identifying microbial features that are associated with clinical efficacy and clearance of AR genes
>18 years;
CRE diagnosed with rectal swab <15 days before evaluation;
Ability to undergo study procedures and to give informed consent.
Active chronic gastrointestinal disorders;
Previous colorectal surgery;
Major comorbidities;
Pregnancy/breastfeeding;
Parallel
Donor - FMT
Biological/Vaccinethis intervention is represented by the administration, in the recipients' gut, of donor microbiota through FMT
Placebo FMT
Other interventionThis intervention is represented by the administration, in the recipients' gut, of a placebo through colonoscopy
CRE eradication at week 4 after the end of treatments
The investigators will evaluate the number of participants who will obtain eradication of CRE carriage after treatments, at 4 weeks-follow-up, evaluated through rectal swab for CRE
CRE eradication at week 1 and 12 after the end of treatments
The investigators will evaluate the number of participants who will obtain eradication of CRE carriage after treatments, at 1,2 and 12 weeks-follow-up, evaluated through rectal swab for CRE
microbiome changes after treatments
The investigators will evaluate microbiome changes through a multi-omic analysis (bacteriome, virome, mycobiome and resistome) . Biocomputational tools and unsupervised machine learning algorithms will be applied to identify microbial features (species, strains, genes, pathways, community structures) that are associated with longitudinal changes in gut resistome and clearance or persistence of AR genes, and link these dynamics to clinical response (eradication of CRE).
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